Tony Hagen is senior managing editor for The Center for Biosimilars

Investigators have demonstrated that initial uptake of the first bevacizumab biosimilar (Mvasi, Amgen) in the United States was strongest for patients receiving treatment for metastatic colorectal cancer (mCRC).

 at the ASCO Gastrointestinal Cancers Symposium 2021, investigators sought to evaluate uptake of Mvasi, which was approved by the FDA for all indications of the reference product (Avastin): mCRC, cervical cancer (CC), non–small cell lung cancer (NSCLC), glioblastoma (GBM), and metastatic renal cell carcinoma (mRCC).

They also concluded that, based on the findings, providers were comfortable initiating or transitioning patients to the bevacizumab biosimilar, and they saw little difference in patient characteristics or demographics between those who previously received the reference product and those who initiated treatment with the bevacizumab biosimilar.

The investigators drew patient data from a Flatiron Health electronic health records database,  Oncology Services Comprehensive Electronic Records, which included cancer treatment information for 2.2 million patients from over 280 cancer clinics. The study included patients who received a bevacizumab biosimilar infusion between July 2019, when Mvasi was first approved, and April 2020 (9 months).

The bevacizumab biosimilar was first used in a patient with mCRC, and this occurred within 10 days of product launch. Ultimately, during the study period, 68% of patients with mCRC received an infusion of Mvasi. The other indications accounted for lower biosimilar use: NSCLC, 14%; GBM, 11%; CC, 5%; and mRCC, 1% (

Patients eligible for inclusion numbered 1657, among whom 685 had no prior reference drug treatment vs 972 who did. The investigators said 49% of patients (810) were younger than 65 years, and 60% were White; 11%, Black; and 2%, Asian. The race distribution between those with no prior reference drug and prior reference drug was equivalent, 84% of patients had Eastern Cooperative Oncology Group (ECOG) scores of 0/1, and median body weight was 78 kg. ECOG is a measure of a patient’s ability to function independently, with 0 representing the highest functioning patients and 5 indicating deceased.

The investigators said 59% of patients with mCRC received the reference product prior to receiving the biosimilar. Among other tumor types, the respective percentages ranged from 42% to 50%.

For 67% of patients with mCRC, the average length of time that elapsed between the last reference drug infusion and biosimilar initiation was ≤ 28 days.

A second bevacizumab biosimilar (Zirabev, Pfizer) was launched in the United States in January 2020. Mvasi was 

at a 15% discount to the reference drug wholesale acquisition cost (WAC; $677 vs $797, respectively) and a 12% average sales price discount (ASP; $677 vs $767). Zirabev was launched at 23% and 19% WAC and ASP discounts, respectively ($613 vs $797 and $613 vs $761, respectively). These sales data, provided in a 2020 report from Amgen, reflect the early 2020 launch of Zirabev and the changes in ASP and WAC that occurred since Mvasi was launched in the third quarter of 2019. 

As of the second quarter of 2020, Mvasi had attained a 38% market share in the United States vs 2% for Zirabev.

Jin R, Accortt NA, Sandschafer D, Lawrence T, Loaiza-Bonilla A. Initial experience of patients treated in a real-world clinical setting with bevacizumab-awwb: the first FDA-approved biosimilar to bevacizumab. Presented at: ASCO GI Cancers Symposium; January 15-17, 2021. Accessed January 15, 2021. https://meetinglibrary.asco.org/record/194163/poster

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ASCO GI 

Investigators looked at the first 9 months of use following the launch of the bevacizumab biosimilar Mvasi to gauge physician comfort with this agent across tumor types.

Swift Uptake for Mvasi Suggests Provider Comfort With Use

Rapid health care reforms in China have led to a regulatory environment that improves conditions for biosimilar development and approval, according to Lawrence A. Hill, PharmD, MBA, RPh, BCPS. Hill is CEO of Gan & Lee Pharmaceuticals, a company specializing in the development and marketing of insulin products in Asia.

Hill, who spoke at the recent Festival of Biologics virtual meeting, said that biosimilars and China go well together because the country has a large “copy” culture in medicine. The country has 382 biologic drugs and vaccines, and just 21 of those are innovative or originator products, he said.

China has supercharged the growth of its biologics industry with a massive health care reform begun in 2008. In 2003, according to the Chinese Ministry of Health, just 55% of urban residents and 21% of rural residents in China had insurance 

. The reform program boosted coverage to 97% of individuals by 2015; however, according to Hill, many of the most expensive medicines still must be paid out-of-pocket. The difficulty many residents of China have in paying for modern medicine makes this a very price sensitive market, which also improves the potential for biosimilar uptake, owing to their cost advantages, he said.

Biosimilars are considered an “integral part” of China’s effort to achieve universal coverage, with the first biosimilar, for rituximab, approved in February 2019. The country has a population of 1.3 billion and its biologics market was the second largest by sales in 2017. This market is also growing fast, with a 16% compound annual growth rate (CAGR) from 2010 to 2021. The market for copy biologics is growing at a 25% CAGR, Hill said.

As a result of the modernization effort, China’s regulatory system for drugs is rapidly coming to resemble the frameworks that have been established in the United States and European Union, Hill said. Priority review for drugs with exceptional clinical value was established in 2016, followed in 2017 by many guidelines for easing acceptance of imported drugs, conditional approvals of urgently needed drugs, and an “orange book” for generic product standards.

Regulatory enhancements from 2018 cover fast approvals for urgently needed foreign drugs. “Companies that can provide evidence of a drug working equally well across races can immediately apply for marketing approval with existing data and be eligible for priority review,” Hill said. Guidelines for accepting overseas clinical trial data and a shortening of the regulatory review period leading to drug approval also came about in 2018. Companies can even move forward with clinical trials if China’s Center for Drug Evaluation (CDE) does not meet preset deadlines for responding with comments, Hill noted.

In 2015, the CDE published final technical guidance for the development and evaluation of copy biologicals. This established principles for research, development, and evaluation of biosimilars, and it defines a biosimilar along lines almost identical to those accepted in the United States and Europe, namely that the drug must be similar in quality, safety, and efficacy and should have an  amino acid sequence that is identical to the originator product.

There are some key differences. Chinese authorities almost always require a comparative clinical efficacy study for a biosimilar, something that regulators may request in the United States or European Union but which in those regions is increasingly considered of little value compared with other biosimilar development groundwork, such as structural and functional characterization and comparative analytical, nonclinical, and clinical stepwise evaluation.

China will not accept a reference product that has been approved by foreign regulators. By comparison, US regulators may accept a foreign reference product if bridging studies are done to demonstrate biosimilarity. There is no established interchangeability policy in China for the substitution of biosimilars for reference products at the pharmacy counter, and the country has no specific standard for biosimilar naming. In the United States, a system of suffixes is applied to approved biosimilars to aid in drug identification and real-world performance tracking.

“The biosimilar regulatory environment in China has been evolving extremely rapidly,” Hill concluded. This has occurred against a backdrop of “exceptionally aggressive” modernization of the pharmaceutical regulatory environment.

Entering the market is challenging for foreign companies, and Hill said the only route of entry for a foreign concern is to partner with a local biopharmaceutical company that can provide guidance and the sponsorship needed for foreign applications. “There are exceptional commercialization opportunities within China. Foreign products are being welcomed,” he said.

Amgen, of Thousand Oaks, California, is one of the outside companies that has taken the 

 of local sponsorship. In 2017, the company partnered with Simcere of Nanjing, China, to codevelop and distribute biosimilars in China for patients with cancer and inflammatory diseases. And in 2019, Samsung Bioepis, of Incheon, Republic of Korea, 

 with the Chinese biopharmaceutical company 3SBio to develop and commercialize biosimilars, including SB8, a bevacizumab biosimilar referencing Avastin.

Some Chinese companies are becoming biosimilar pioneers in their own right. These include Henlius, Innovent, Bio-Thera, and Hisun Pharmaceuticals. Henlius obtained the first biosimilar approval in China and has a large pipeline of products. The company most recently reported Chinese regulatory acceptance for HLX03, an 

 biosimilar for the treatment of rheumatoid arthritis, ankylosing spondylitis, and plaque psoriasis. This marks the third biosimilar approval in China for Henlius.

Hill’s company, Gan & Lee, was founded as Beijing Gan & Lee Biotechnology and developed the first recombinant human insulin (Gansulin) in China.

Festival of Biologics Basel

Lawrence A. Hill, PharmD, MBA, RPH, BCPS, provided an insider's view of the rapidly changing biologics and biosimilars market and regulatory structure in China. 

Hill Describes Supercharged Biologics Market in China

Investigators have reported pharmacokinetic (PK) findings that confirm the biosimilarity of Viatris’ trastuzumab biosimilar candidate (MYL-14010, Ogivri) to reference Herceptin. Ogivri, developed by Mylan, which is now Viatris, was approved by the FDA in 2017.

 randomized phase 3 study, which previously demonstrated comparable efficacy and safety for Ogivri vs Herceptin as frontline treatment for women with human epidermal growth factor receptor 2 (HER2)–positive advanced breast cancer. The biosimilar was launched in the United States in December 2019, and these latest findings were presented at the 2020 San Antonio Breast Cancer Symposium (SABCS).

Patients (N = 485) were randomized to receive the biosimilar (n = 245) or reference product (n = 240) in combination with a taxane (docetaxel or paclitaxel) every 3 weeks for 24 weeks for 8 cycles, followed by additional cycles of monotherapy until disease progression, discontinuation, or unacceptable toxicity.

Primary objectives of the study were to compare drug concentration variation (area under the curve), maximum serum drug concentration, clearance (drug elimination), drug propensity to leave the plasma (volume of distribution), and terminal elimination half-life (no further drug distribution or absorption).

The investigators also sought to assess shed extracellular domain (ECD) HER2 receptor fragments and their effect on PK parameters. The decrease of shed ECD HER2 fragments is associated with an improved prognosis in metastatic breast cancer.

They took PK samples from patients at cycles 1, 2, 4, 6, 8, and 9 (monotherapy) to assess minimum serum concentrations. Serum maximum concentration samples were collected at the end of cycles 1 and 6. Additional samples were collected from a population subset. The final analysis included 213 patients in the biosimilar group and 202 in the Herceptin group.

No notable differences in demographics were observed between the 2 patient cohorts, the investigators said, noting there were no dissimilarities in trastuzumab concentrations between the groups. Treatment (biosimilar or reference) was not a significant covariate of clearance (

However, ECD HER2 concentration was a significant factor in trastuzumab clearance, and weight was also a significant covariate of clearance and drug distribution (volume of the central compartment).

In the trough concentration (lowest drug concentration before the next dose) analysis, data were comparable between treatment arms at the end of cycles 1 and 6, the investigators said (

They used Bayesian statistics to evaluate steady state drug exposure between treatment arms and found comparable results indicating PK biosimilarity between the biosimilar and reference drugs. Steady state represents equivalent rates of drug absorption and elimination.

A low frequency of antidrug antibodies, which counteracts the effects of trastuzumab, were observed between Ogivri (n = 14) and Herceptin (n = 21).

Investigators concluded the population PK profiles of Ogivri vs Herceptin were comparable in patients with HER2-positive metastatic breast cancer. They said the study confirmed earlier PK findings.

Financial support for the study and its presentation at SABCS was provided by Viatris, investigators said.

Owen J, Rackley R, Liu M, et al. Population pharmacokinetics of MYL-14010 (a trastuzumab biosimilar) and reference trastuzumab (Herceptin) in patients with HER2-positvie metastatic breast cancer. Poster presented at: SABCS; December 8-11, 2020. PS18-23. https://sabcs.onlineeventpro.freeman.com/single-file-viewer/25581567

San Antonio Breast Cancer Symposium

Pharmacokinetic (PK) parameters matched up with those of reference trastuzumab in an extended analysis of data from the HERITAGE trial. 

Data From HERITAGE Confirm PK Biosimilarity for Ogivri

A study of the trastuzumab biosimilar ABP 980 (Kanjinti) in Europe found strong uptake patterns, according to an abstract presentation at the 2020 San Antonio Breast Cancer Symposium.

ABP 980 is approved in Europe and the United States for the treatment of human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer and metastatic gastric cancer. Investigators sought to understand the real-world application of this product in clinical treatment of patients with breast cancer.

They enrolled patients 18 years or older with a history of breast cancer of any disease or treatment phase, seeking primarily to understand patient demographics and disease characteristics. Exploratory end points included cardiac dysfunction, infusion-related problems, other adverse events, and other safety issues. Efficacy  was a secondary end point.

Enrollment included 135 women from Poland, Italy, the Netherlands, France, and Spain, mostly from hospital sites, both academic and public or private. The mean patient age was 58.3 years. 

The investigators said 28% of sites had policies on biosimilar use and that 36% of patients were informed they were being started on a biosimilar, with 34% being notified what brand of biosimilar would be used. Twenty-two percent, 27%, 13%, and 28% of patients had stage I, II, III, or IV disease, respectively, at the time ABP 980 was initiated. They also said 68% of patients had estrogen/progesterone receptor–positive tumors. All patients (n = 73) who had been evaluated for Eastern Cooperative Oncology Group performance  had a score of 0 or 1.

There was roughly equal use of ABP 980 across treatment settings: neoadjuvant, 39%; adjuvant 30%; and metastatic, 30%.

Among patients who received treatment for metastatic breast cancer (n = 41), 56% and 20% received it for frontline and second-line treatment, respectively. The investigators said that 40% (n = 54) of patients switched to ABP 980 from another trastuzumab product. Of those, 44% switched from the intravenous form of the originator biologic and 15% switched from the subcutaneous form. Most who switched to the subcutaneous form were receiving treatment for metastatic disease.

The investigators concluded there was ABP 980 “uptake across a mixture of institution types and breast cancer treatment settings, including those with curative potential.” The study is ongoing.

Kufel-Grabowska J, San T, Bernardo A, et al. Patterns of use of a trastuzumab biosimilar (ABP 980) in patients with HER2+ breast cancer treated in clinical practice in Europe: An interim analysis from an observational chart review study (GARDENIA). Poster presented at: San Antonio Breast Cancer Symposium; December 8-11, 2020. PS10-50. 

Among patients treated for metastatic breast cancer, 40% switched to ABP 980. 

Investigators Chart ABP 980 Biosimilar Uptake in European Clinics

Investigators studying trastuzumab biosimilar savings and use rates across different disease settings in human epidermal growth factor receptor 2 (HER2)-positive breast cancer observed dramatically increased usage of biosimilars and said payer policy appears to have contributed to higher biosimilar utilization.

They looked at treatment plans submitted for patients to determine usage rates for originator vs biosimilar trastuzumab and trastuzumab in combination with hyaluronidase-oysk. The average costs of originator and biosimilar trastuzumab per patient cycle were $4502 and $3618, respectively, with an average savings per biosimilar dose (440 mg, trastuzumab; 600 mg trastuzumab hyaluronidase) of $884. Total savings for 4502 patients with stage I to III disease was $24.4 million, according to the 

 presentation at the 2020 San Antonio Breast Cancer Symposium (SABCS).

Of 6657 treatment plans submitted for 4505 patients with stage 0 to III disease, the biosimilar usage rate was 34% (n = 2271 treatment plans). Investigators said that for 3312 plans submitted for 1933 patients with stage IV/recurrent disease, the biosimilar usage rate was 27% (n = 904 treatment plans).

The treatment plan submissions were tracked from June 2019 to October 2020 and showed a dramatic increase in biosimilar adoption. For patients with stage I to III disease, trastuzumab biosimilar use was 1.4% in the third quarter of 2019 vs 65.9 % in the fourth quarter of 2020. For patients with stage IV/recurrent disease, usage climbed from 1.6% to 49.3%, respectively.

Some patients had multiple treatment plans based on receipt of adjuvant or neoadjuvant therapy, treatment for local or recurrent disease, or metastatic/recurrent therapy. Patients with stage I to III disease were assumed to receive 1 year (18 doses) of trastuzumab therapy. Those with stage IV/recurrent disease were assumed to receive 11 months (16 cycles) of treatment.

The investigators said there was evidence that biosimilar use increased based on payer policies that favored biosimilars. Biosimilar use was 41.5% where payer policies were favorable vs 30.9% when that was not the case.

”As biosimilars were being introduced at different times during this time period and payer policy would likely lag behind these introductions, it is likely that the observed difference in biosimilar use by payer policy is underestimated,” the authors of the study wrote.

They concluded that the potential savings from biosimilar trastuzumab in breast cancer are “significant. Future estimates should use more rigorous models with stratification by use with hormonal therapy, chemotherapy, combinations with pertuzumab, or single agent, and the corresponding durations of therapy,” the authors recommended.

Flood WA, Avery T, Kozlovsky V, Margolis N, Reddy SK. Real world data on the adoption of trastuzumab biosimilars in the treatment of HER2-positive breast cancer. Poster presented at: SABCS; December 8-11, 2020. PS9-63. https://sabcs.onlineeventpro.freeman.com/single-file-viewer/25582299

In little over 1 year of use in patients with breast cancer, trastuzumab biosimilars have seen rapid growth in uptake. 

Investigators Demonstrate Dramatic Rise in Trastuzumab Biosimilar Use

Studies of trastuzumab biosimilars in human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC) have yielded significant findings, according to presentations at the 2020 San Antonio Breast Cancer Symposium.

Investigators achieved a 45.5% response rate in patients with HER2-positive mBC and 

 aberrations who were treated with the trastuzumab biosimilar Herzuma and an experimental PIK3CA pathway inhibitor (gedatolisib, PF-05212384) in a phase 2 pilot trial.

 pathway aberrations tend to promote tumor cell growth and survival despite treatment with monoclonal antibodies, chemotherapy, and radiotherapy. The study authors hypothesized the combination of trastuzuamb and gedatolisib would improve outcomes for select patients with disease progression who had exhausted approved treatment options for mBC.

They enrolled 15 patients with HER2-positive mBC with a known 

) and who had failed on multiple prior lines of therapy. Patients received a trastuzumab biosimilar 8 mg/kg intravenously for the first cycle and then 6 mg/kg every 3 weeks plus gedatolisib 180 mg on days 1, 8, and 15 every 21 days.

As of the data cutoff on August 4, 2020, 11 patients were eligible for response assessment. Five achieved partial response as their best response; 3, stable disease; and 3, progressive disease. All patients with partial response remain on the investigational treatment, with the longest term being 7.8 months. Among the patients with stable disease, 1 discontinued due to disease progression and 2 continue to receive therapy. The investigators said the disease control rate was 72.7% with no treatment-related fatal adverse events.

A multicenter, global, phase 3 study of the trastuzumab biosimilar MYL-1401O (Ogivri) in patients with HER2-positive mBC has demonstrated pharmacokinetic (PK) equivalence between the biosimilar and the reference product (Herceptin).

by the FDA in December 2017 and marketed in the United States December 2019.

Investigators randomized 485 patients 1:1 to receive the biosimilar or reference product, with the aim of assessing biosimilarity on the basis of efficacy, safety, population PK, and immunogenicity. They said 482 patients were included in the population PK analysis.

The measures for drug exposure at or near steady-state dosing were comparable for Ogivri and the reference drug, demonstrating PK biosimilarity, the investigators said. Steady state is the time the concentration of the drug in the body stays consistent during administration, with the amount of drug entering the patient’s system being equivalent to the rate of elimination.

Other measures of PKs also supported equivalence, they said. “Population PK profiles of [Ogivri] vs Herceptin were similar in patients with HER2-positive mBC. Model-based exposure measures were similar between treatments.”

They added that extracellular domain fragments of the HER2 receptor “were a strong determinant of trastuzumab clearance [elimination], and clearance was similar between [biosimilar and reference drug] treatments.” They observed that trough concentrations—drug concentrations immediately before the next dose—were similar between treatments at the end of cycle 1 and at cycle 6.

1. Kim JW, Ahn HK, Choi JG, et al. Phase II pilot study of trastuzumab biosimilar (Herzuma) plus gedatolisib in patients with HER-2 positive metastatic breast cancer who progressed after 2 or more HER-2 directed chemotherapy [KM-10A/KCSG18-13 interim analysis]. Presented at: SABCS; December 8-11, 2020. Abstract PS11-39. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

2. Owen J, Rackley R, Liu M, et al. Population pharmacokinetics (pop PK) of MYL‑1401O (a trastuzumab biosimilar) and reference trastuzumab (Herceptin) in patients with HER2‑positive metastatic breast cancer (mBC). Presented at: SABCS; December 8-11, 2020. Abstract PS18-23. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

Two studies of trastuzumab biosimilars have improved understanding of these medicines as monotherapy and in combination with other agents in metastatic breast cancer.

Trastuzumab Biosimilar With PIK3CA Inhibitor Shows Efficacy in Advanced Breast Cancer

Investigators hope to improve durability of response in human epidermal growth factor receptor 2 (HER2)-positive solid tumors with a novel trastuzumab biosimilar conjugated to a toll-like receptor 7/8 agonist and designed to activate myeloid antigen presenting cells, which alert T cells to the presence of cancerous cells and mediate an immune response.

The investigational biosimilar (BDC-1001) holds potential as an improvement on anti-HER2 monoclonal antibodies in HER2-driven or -expressing cancers. In studies of mice with tumors resistant to conventional treatment, trastuzumab-based immune-stimulating antibody conjugates have elicited potent and durable antitumor efficacy “including complete tumor regression,” investigators said in an 

 presented at the 2020 San Antonio Breast Cancer Symposium.

“Importantly, BDC-1001 did not induce interstitial lung disease, cytokine release syndrome, or thrombocytopenia in primate studies," the investigators said.

The phase 1/2, first-in-human, dose-escalation and dose-expansion study will enroll up to 390 patients with HER2-expressing or HER2-amplified advanced solid tumors who have exhausted the potential for treatment with approved anti-HER2 treatments. Patients will receive BDC-1001 with or without an immune checkpoint inhibitor targeting PD-1.

The dose-escalation phase of the trial will help to determine safety and tolerability of the treatment and establish the phase 2 dose of BDC-1001 as monotherapy and in combination with an immune checkpoint inhibitor. Primary end points include incidence of adverse events, dose-limiting toxicities, and potential immune-related toxicities.

Patients will receive BDC-1001 intravenously every 3 weeks in increasing doses. The completion of the safety data portion of the trial will allow investigators to proceed with the immune checkpoint inhibitor combination component. The dose-expansion portion of the trial will evaluate both the monotherapy with BDC-1001 and the investigational agent in combination with a checkpoint inhibitor. The primary end point of the dose-expansion portion is overall response rate.

The investigators also hope to elucidate the mechanism of action for BDC-1001 and identify biomarkers to help improve selection of patients most likely to benefit from the treatment with and without checkpoint inhibitors.

Dumbrava EI, Sharma MR, Carvajal RD, et al. Phase 1/2 study of a novel HER2 targeting TLR7/8 immune-stimulating antibody conjugate (ISAC), BDC-1001, as a single agent and in combination with an immune checkpoint inhibitor in patients with advanced HER2-expressing solid tumors. Presented at: SABCS; December 8-11, 2020. Abstract OT-03-02. www.sabcs.org/portals/sabcs2016/2020%20SABCS/Final%20PDF%20Docs%20111620_All%20PDF%20File%20No%20Embargoed%20Abstracts.pdf

Investigators explained the potential for durable antitumor efficacy in patients with human epidermal growth factor receptor 2 (HER2)-expressing or -driven tumors who have exhausted other treatment options.

Biosimilar Conjugate Evaluated in HER2-Positive Patient Population

A single-center, retrospective data analysis in India evaluating safety and efficacy of biosimilar romiplostim (Romy) in patients with immune thrombocytopenic purpura (ITP) has demonstrated a high overall response rate (93%) without adverse events.

Romiplostim (Nplate) received US approval in 2008 for the treatment of ITP, which is characterized by an immune system attack on platelets that results in bruising, bleeding, and reddish-purple spots on the lower legs. The biosimilar Romy is 

Investigators enrolled 54 patients (male, 23; female, 31; median age, 40 years) with steroid-refractory or steroid-dependent ITP at the Haemato-Oncology Care Center in Vadodara, India, from July 2019 to January 2020. All patients had a pretreatment platelet count of less than 30,000/cmm. Romiplostim biosimilar was administered in a dose of 1 mcg/kg to 6 mcg/kg subcutaneously once a week.

Roughly 20% of patients (n = 12) had active bleeding and also received a concomitant rituximab 100 mg infusion once weekly for 4 weeks. For 51 patients, the overall response rate (ORR) with platelet count above 50,000 cmm; 4 patients (7%) had no response. Among patients who received rituximab with romiplostim, the ORR was 100% (12).

Investigators said the time to response was 1 week in 85% (46) of patients, and 16% (9) had a sustained response lasting more than 6 months even after discontinuing romiplostim at 4 weeks of therapy. They said 40% (21) had a sustained optimum response lasting more than 6 months with uninterrupted treatment. No patients experienced serious adverse events.

“Biosimilar romiplostim has shown rapid, excellent, and sustained response in the majority of ITP patients in our study,” said Seema S. Bhatwadekar, MD, MBBS, lead study author. “Its affordable cost [$160 per month] fulfills an unmet need for ITP patients requiring the best second line of treatment in India.”

Bhatwadekar SS, Deshpande SV, Khadse SV, et al. Efficacy and safety of biosimilar romiplostim in immune thrombocytopenic purpura: single centre retrospective data analysis. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Abstract 2676.

American Society of Hematology  Annual Meeting and Exposition

A high overall response rate of 93% was observed for patients with immune thrombocytopenic purpura who received romiplostim biosimilar. 

Romiplostim Biosimilar Study Demonstrates Safety, Efficacy in Real-World India Population

Investigators said they were able to demonstrate the biosimilarity of a rituximab biosimilar (CT-P10 [Truxima]) to reference rituximab in a long-term (27 months) efficacy and safety study (N = 258) involving a single transition from the originator to the biosimilar in patients with low–tumor burden follicular lymphoma (LTBFL). CT-P10 is a Celltrion biosimilar that was approved by the FDA in November 2018 for patients with CD20-positive, B-cell non-Hodgkin lymphoma.

The trial was a randomized (1:1), controlled, double-blind, phase 3 study in LTBFL. Patients received CT-P10 (375 mg/m

) weekly or the reference product at the same dose for an induction period of 4 cycles, followed by maintenance treatment once every 2 months for 2 years. The primary end point was overall response rate (ORR) over 7 months, defined as the number of patients achieving complete response (CR), unconfirmed complete response, or partial response. The secondary end point was ORR during the study period, overall survival (OS), progression-free survival (PFS), and time to progression.

Most patients completed induction and initiated maintenance period 1 (CT-P10, n = 123; reference, n = 120). Reasons for treatment discontinuation were similar between treatment groups, with the most frequently reported reason in both groups being progressive disease.

Investigators reported no clinically meaningful differences in ORR or OS between treatment cohorts over the study period. The ORR was 88% (n = 115) in the CT-P10 cohort and 87% (n = 111) in the rituximab reference group. This included CR rates of 56% and 52% for the CT-P10 and rituximab reference groups, respectively.

Median PFS was not estimable in either group due to a low number of events. The investigators stressed caution in interpreting the significance of this “due to the relatively immature data set.” There was no difference in OS between groups, although median OS also was not estimable.

The investigators said 88% and 81% of patients in the CT-P10 and reference groups, respectively, experienced at least 1 treatment emergent adverse event, and 11% of patients in each group experienced treatment emergent serious adverse events. “There were no unexpected safety signals … after the single transition from rituximab [reference] to CT-P10,” said Larry W. Kwak, MD, PhD, lead author, City of Hope, Duarte, California.

“The overall similarity in ORR, OS, and safety over the study period supports the biosimilarity between the CT-P10 and rituximab [products]," Kwak said, adding that longer-term follow-up is needed to understand the efficacy findings.

Kwak LW, Sancho JM, Cho SG, et al. Long-term efficacy and safety (27 months) of the biosimilar CT-P10 in patients with low tumor burden follicular lymphoma. Presented at: 62nd American Society of Hematology Annual Meeting and Exposition; December 5-8, 2020. Poster 1125. https://ash.confex.com/ash/2020/webprogram/Paper135999.html

A long-term, comparative, phase 3 trial of CT-P10 vs the rituximab originator product has provided evidence of biosimilar value in this blood disorder.

Celltrion's Rituximab Biosimilar Demonstrates Equivalence in Follicular Lymphoma

In a pair of simulation studies utilizing pegfilgrastim originator products and biosimilars, investigators set out to calculate the savings possible from switching to biosimilars and what could be achieved with those savings in terms of additional treatment. They found significant savings potential and concluded that hospitalization costs could be lowered by switching to biosimilar pegfilgrastim from the pegfilgrastim on-body injector (OBI).

The studies are due to be presented at the upcoming American Society of Hematology Annual Meeting and Exposition, December 5 to 8, 2020.

In one of the studies, investigators simulated the potential savings for a population of 20,000 patients with non-Hodgkin lymphoma.

 Based on average sales price (ASP) of the agents in question, they found that total savings of $371,444 were possible for the hypothetical patients if 10% were converted to pegfilgrastim biosimilar (Udenyca) from reference product or OBI and received 1 cycle of the prophylactic treatment (to prevent incidence of chemotherapy-induced febrile neutropenia). If 100% of patients were converted and received 6 cycles of treatment of the biosimilar, the potential savings climbed to $22.3 million.

Using a blended ASP, wholesale acquisition cost (WAC) basis, investigators said the potential savings in a single cycle of chemotherapy meant it was possible to expand access to Udenyca by 524 cycles at a 10% conversion rate and 5243 cycles at 100% conversion. They said 4 patients would have to be converted to purchase 1 additional cycle of biosimilar pegfilgrastim.

To pay for an additional cycle of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP), 8 patients would need to be converted from 1 cycle of reference pegfilgrastim to Udenyca, they said. This calculation was also based on the ASP/WAC blended rate. Investigators said expanded access to R-CHOP ranged from 282 cycles at 10% conversion to 2817 cycles at 100% conversion for patients who received a single cycle of chemotherapy. Over multiple cycles, the savings were potentially much higher.

“These simulation models demonstrate that significant cost savings for supportive cancer care can be generated through conversion,” they wrote.

In the second study, investigators found that pegfilgrastim biosimilar (Fulphila) used as prophylaxis for chemotherapy-induced febrile neutropenia has savings and access advantages over pegfilgrastim originator product delivered via the OBI, which is available only for the reference product.

The OBI has seen elevated usage during the coronavirus disease 2019 pandemic because it enables patients to receive doses outside the clinic, which is considered convenient and safe. However, investigators noted that the OBI has a failure rate of 1.7% to 6.9% that “predisposes patients to increased risk” of chemotherapy-related febrile neutropenia. These failures lead to hospitalizations. Cost savings generated from conversion to biosimilar pegfilgrastim (Fulphila) would create opportunities for expanded access, they wrote.

Investigators did a simulation analysis involving a cohort of 15,000 patients with diffuse large B-cell lymphoma at risk for febrile neutropenia. They said that after accounting for hospital costs related to OBI failure, the potential savings from the first cycle of prophylaxis at 10% conversion to the biosimilar were $406,118. This was based on an OBI failure rate of 1%. The savings climbed significantly based on additional cycles of treatment and higher assumed OBI failure rates. 

Investigators said the savings translated into expanded access of 118 additional cycles of Fulphila or 62 cycles of R-CHOP, also at 10% conversion with a 1% OBI failure rate.

Prophylaxis with Fulphila generated substantial cost savings compared with OBI ($379,230; 1 cycle of prophylaxis at 10% conversion), the investigators wrote. They concluded that biosimilar savings further increased when the costs of febrile neutropenia–related hospitalization from pegfilgrastim OBI failure were factored in.

1. McBride A, MacDonald K, Abraham I. Simulation modeling of cost-savings from conversion to biosimilar pegfilgrastim-cbqv for the prophylaxis of chemotherapy-induced neutropenia, and budget-neutral expanded access to prophylaxis and anti-neoplastic therapy from derived cost-savings in non-Hodgkin lymphoma. Presented at: 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. Abstract 3425.

2. McBride A, MacDonald K, Abraham I. Conversion to biosimilar pegfilgrastim-jmdb from pegfilgrastim with on-body injector device in diffuse large B-cell lymphoma: simulation modeling of cost-savings and budget-neutral expanded access to prophylaxis and anti-neoplastic therapy considering device failure rate. Presented at: 62nd ASH Annual Meeting and Exposition; December 5-8, 2020. Abstract 3422.

The wearable injector has a failure rate that adds hospitalization costs; therefore, biosimilar pegfilgrastim may hold cost advantages, investigators conclude. 

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